G.M. Antón-Fos

Use of topological descriptiors in chromatographic chiral separations

Abstract Studies of enantiomeric separations are reported, specifically the direct chromatographic separation of enantiomers using a chiral stationary phase by molecular topology. The results obtained show good correlation equations for the capacity factor, k ′, and the separation factor, α, for different set of compounds (hydantoins, aromatic α-amino acids and arylamides). Such equations may be useful for the selection of the optimum stationary and mobile phases for the separation of enantiomers. Futher, the correlation between topological descriptors and performance in chiral separations opens up a new approach to the design of chiral stationary phases.

Search of a topological pattern to evaluate toxicity of heterogeneous compounds.

Abstract Molecular connectivity has been applied to the search of mathematical models able to predict the carcinogenic and teratogenic activity of a wide group of structurally heterogeneous compounds. Through the linear discriminant analysis and the diagrams of distribution of pharmacological activity, the classification criteria that minimizes the percentage of error are established. The easiness and speed of the calculation of the descriptors used in this work make the models developed useful in data bases containing a huge number of compounds.

Prediction of chromatographic properties for a group of natural phenolic derivatives by molecular topology

A study was made of the relationship between the RM values obtained by thin-layer chromatography for a group of phenols and connectivity indices proposed by Kier and Hall. By using multivariate regression the corresponding connectivity functions were obtained, which were selected based on their respective statistical parameters. Regression analysis of the connectivity functions showed a correct prediction of the experimental elution sequence for this group of molecules using silica gel stationary phases and mobile phases of different polarity. Random and stability studies of the different prediction models selected were carried out, and good stability and null randomness were obtained in all cases.

Use of molecular topology for the prediction of physico-chemical, pharmacokinetic and toxicological properties of a group of antihistaminic drugs

We used molecular connectivity to search mathematical models for predicting physico-chemical (e.g. the partition coefficient, P), pharmacokinetic (e.g. the time of maximum plasma level, and toxicological properties (lethal dose, LD) for a group of antihistaminic drugs. The results obtained clearly reveal the high efficiency of molecular topology for the prediction of these properties. Randomization and cross-validation by use of leave-one-out tests were also performed in order to assess the stability and the prediction ability of the connectivity functions selected.

Calculation of chromatographic parameters by molecular topology : sulphamides

This investigation was undertaken to test the ability of the molecular connectivity model to predict RF values in thin-layer chromatography (TLC) for a group of sulphamides using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, F-Snedecor function values and Students t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts the values for this property in different silica gel stationary phases and different polar mobile phases. Corresponding stability and random studies were made on the selected prediction models which confirmed their goodness of fit. The results also demonstrated that different structural features determine the RF values in TLC of sulphamides.

Prediction of chromatographic parameters for some anilines by molecular connectivity

SummaryThe possible relation existing between RF values obtained by thin-layer chromatography for a group of anilines with connectivity indices proposed by Kier and Hall has been studied. Using multivariable regression the corresponding connectivity functions, selected for their respective correlation coefficients, standard deviations, Snedecor’s F and Student’s t were obtained. Regression analysis of the connectivity functions gives a correct prediction of the experimental elution sequence for this group of substances on silica gel stationary phases and various mobile phases of different polarity. The corresponding random and stability studies of the different prediction models selected were carried out, showing good stability and null randomness in all cases.

Prediction of chromatographic properties of organophosphorus insecticides by molecular connectivity

SummaryA study is reported of the relationship between theRF values for a group of organophosphorus insecticides obtained by thin layer chromatography and a series of topological descriptors. By using multivariate regression, the corresponding connectivity functions were obtained, which had been selected on the basis of their respective statistical parameters: multiple correlation coefficient (r), standard error of estimate (s), F-Snedecor values and statistical significance (Student’s t). Regression analysis of the connectivity functions can predict the elution behaviour of any structurally similar derivative of this group of compounds with different stationary and mobile phases. Stability studies of the prediction models selected were carried out and yielded good stability in all cases. These results demonstrate the ability of Molecular Topology to identify and predict different structural features that determine theRF values of organophosphorus insecticides obtained by TLC.

Correlation of Pharmacological Properties of a Group of β-Blocker Agents by Molecular Topology

The molecular connectivity method has been applied to the study of pharmacological properties, among which are found the angor treatment dose, α‐distribution half‐life and intravenous LD50 in mouse, of a group of β‐blocker agents, verifying its application in the prediction of theoretic values for said pharmacological properties.

Calculation of chromatographic properties of barbiturates by molecular topology

SummaryA study has been made of the relationship between the RF values obtained by thin layer chromatography for a group of barbiturates and the connectivity indices proposed by Kier and Hall. By using multivariable regression we obtained the corresponding connectivity functions, which were selected on the basis of their respective statistics parameters. The regression analysis of the connectivity functions shows a correct prediction of the experimental elution sequence for this group of molecules on silicagel with two mobile phases of different polarity. The corresponding random and stability studies of the different prediction models selected were carried out, demonstrating good stability and null randomness in all cases. The results also demonstrated that different structural features determine the RF values in TLC of barbiturates.

Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology

This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi‐variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F‐Snedecor function values, Mallows CP and Students t‐test as criteria of fit.